Brain-Computer Interfaces in Medicine Shih, Jerry J., MD; Krusienski, Dean J., PhD; Wolpaw, Jonathan R., MD
Mayo Clinic proceedings,
03/2012, Letnik:
87, Številka:
3
Journal Article
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Abstract Brain-computer interfaces (BCIs) acquire brain signals, analyze them, and translate them into commands that are relayed to output devices that carry out desired actions. BCIs do not use ...normal neuromuscular output pathways. The main goal of BCI is to replace or restore useful function to people disabled by neuromuscular disorders such as amyotrophic lateral sclerosis, cerebral palsy, stroke, or spinal cord injury. From initial demonstrations of electroencephalography-based spelling and single-neuron-based device control, researchers have gone on to use electroencephalographic, intracortical, electrocorticographic, and other brain signals for increasingly complex control of cursors, robotic arms, prostheses, wheelchairs, and other devices. Brain-computer interfaces may also prove useful for rehabilitation after stroke and for other disorders. In the future, they might augment the performance of surgeons or other medical professionals. Brain-computer interface technology is the focus of a rapidly growing research and development enterprise that is greatly exciting scientists, engineers, clinicians, and the public in general. Its future achievements will depend on advances in 3 crucial areas. Brain-computer interfaces need signal-acquisition hardware that is convenient, portable, safe, and able to function in all environments. Brain-computer interface systems need to be validated in long-term studies of real-world use by people with severe disabilities, and effective and viable models for their widespread dissemination must be implemented. Finally, the day-to-day and moment-to-moment reliability of BCI performance must be improved so that it approaches the reliability of natural muscle-based function.
Targeting the tumor vasculature with antibody-drug conjugates (ADCs) is a promising anti-cancer strategy that in order to be realized must overcome several obstacles, including identification of ...suitable targets and optimal warheads. Here, we demonstrate that the cell-surface protein CD276/B7-H3 is broadly overexpressed by multiple tumor types on both cancer cells and tumor-infiltrating blood vessels, making it a potentially ideal dual-compartment therapeutic target. In preclinical studies CD276 ADCs armed with a conventional MMAE warhead destroyed CD276-positive cancer cells, but were ineffective against tumor vasculature. In contrast, pyrrolobenzodiazepine-conjugated CD276 ADCs killed both cancer cells and tumor vasculature, eradicating large established tumors and metastases, and improving long-term overall survival. CD276-targeted dual-compartment ablation could aid in the development of highly selective broad-acting anti-cancer therapies.
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•CD276/B7-H3 is broadly overexpressed in both cancer cells and tumor vasculature•Both angiogenic and non-angiogenic tumor vasculature express CD276•Anti-CD276-drug conjugates display potent anti-tumor and anti-metastatic activity•Pyrrolobenzodiazepine dimers are optimal warheads for targeting tumor vasculature
Seaman et al. show that CD276 is broadly overexpressed in cancer cells and tumor vascular cells and demonstrate anti-CD276-drug conjugates as promising anti-cancer reagents. The drug selected for conjugation is important because tumor vascular cells can be resistant to a drug to which tumor cells are sensitive.
PARP-1 is an abundant nuclear enzyme that modifies substrates by poly(ADP-ribose)-ylation. PARP-1 has well-described functions in DNA damage repair and also functions as a context-specific regulator ...of transcription factors. With multiple models, data show that PARP-1 elicits protumorigenic effects in androgen receptor (AR)-positive prostate cancer cells, in both the presence and absence of genotoxic insult. Mechanistically, PARP-1 is recruited to sites of AR function, therein promoting AR occupancy and AR function. It was further confirmed in genetically defined systems that PARP-1 supports AR transcriptional function, and that in models of advanced prostate cancer, PARP-1 enzymatic activity is enhanced, further linking PARP-1 to AR activity and disease progression. In vivo analyses show that PARP-1 activity is required for AR function in xenograft tumors, as well as tumor cell growth in vivo and generation and maintenance of castration resistance. Finally, in a novel explant system of primary human tumors, targeting PARP-1 potently suppresses tumor cell proliferation. Collectively, these studies identify novel functions of PARP-1 in promoting disease progression, and ultimately suggest that the dual functions of PARP-1 can be targeted in human prostate cancer to suppress tumor growth and progression to castration resistance.
These studies introduce a paradigm shift with regard to PARP-1 function in human malignancy, and suggest that the dual functions of PARP-1 in DNA damage repair and transcription factor regulation can be leveraged to suppress pathways critical for promalignant phenotypes in prostate cancer cells by modulation of the DNA damage response and hormone signaling pathways. The combined studies highlight the importance of dual PARP-1 function in malignancy and provide the basis for therapeutic targeting.
The role of incentive mechanisms in promoting forest restoration Tedesco, Anazelia M; Brancalion, Pedro H S; Hepburn, Michelle L Hak ...
Philosophical transactions of the Royal Society of London. Series B. Biological sciences,
01/2023, Letnik:
378, Številka:
1867
Journal Article
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Forest restoration has been proposed as a scalable nature-based solution to achieve global environmental and socio-economic outcomes and is central to many policy initiatives, such as the Bonn ...Challenge. Restored forests contain appreciable biodiversity, improve habitat connectivity and sequester carbon. Incentive mechanisms (e.g. payments for ecosystem services and allocation of management rights) have been a focus of forest restoration efforts for decades. Yet, there is still little understanding of their role in promoting restoration success. We conducted a systematic literature review to investigate how incentive mechanisms are used to promote forest restoration, outcomes, and the biophysical and socio-economic factors that influence implementation and program success. We found that socio-economic factors, such as governance, monitoring systems and the experience and beliefs of participants, dominate whether or not an incentive mechanism is successful. We found that approximately half of the studies report both positive ecological and socio-economic outcomes. However, reported adverse outcomes were more commonly socio-economic than ecological. Our results reveal that achieving forest restoration at a sufficient scale to meet international commitments will require stronger assessment and management of socio-economic factors that enable or constrain the success of incentive mechanisms. This article is part of the theme issue 'Understanding forest landscape restoration: reinforcing scientific foundations for the UN Decade on Ecosystem Restoration'.
The positive influence of urban green spaces on human health and well‐being is well known while the pathways are little understood. Past research has largely focused on visual stimuli, yet the ...auditory pathway is also an important means for contact with nature.
The sonic environments of urban green spaces, however, are rarely entirely natural and many differ in their composition of natural sounds and anthropogenic noise. Few studies have investigated how these differences may impact the restorative potential of these soundscapes and, in particular, how the presence of traffic noise may constrain the benefits of natural sounds.
To address this gap, we examined differences in the perceived restorativeness and perceived restorative outcomes across a gradient of eight park soundscapes that differed in bird and traffic sounds. In a laboratory setting, 162 participants listened to sound samples and reported on perceptions of the soundscapes and restorative potential and outcomes.
The results strongly indicate that park soundscapes with a rich array of perceived bird sounds and minimal perceived traffic noise offer the greatest perceived restoration. Traffic noise was found to moderate the positive effect of bird sounds. The duration of time lived in the city and noise sensitivity were also positively associated with greater perceived restorative benefits while noise‐sensitive people were also more negatively affected by traffic noise.
The promotion of highly natural soundscapes in urban green spaces and the reduction of traffic noise can provide nature‐based solutions to human health and well‐being in urban areas.
A free Plain Language Summary can be found within the Supporting Information of this article.
Prostaglandin E1 (PGE) is used in patients with ductal-dependent congenital heart disease (CHD). Side effects of apnea and fever are often dose dependent and occur within 48 h after initiation. We ...initiated a standardized approach to PGE initiation after our institution recognized a high incidence of side effects and a wide variety of starting doses of PGE. Neonates with prenatally diagnosed ductal-dependent CHD were identified, started on a standardized protocol that started PGE at 0.01 mcg/kg/min, and evaluated for PGE related side effects. Compliance, outcomes and dose adjustments during the first 48 h post-PGE initiation were evaluated. Fifty patients were identified (25 pre-intervention; 25 post-intervention). After intervention, compliance with the protocol was 96%, and apnea or fever occurred in 28% (compared to 63% pre-intervention,
p
= 0.015). Dose adjustments (either increase or decrease) prior to cardiac surgery were similar in both cohorts (60%, 52%,
p
= 0.569). There were no mortalities or emergent procedures performed due to ductus arteriosus closure. Standardizing a protocol for initiating PGE in prenatally diagnosed ductal-dependent CHD was successful and reduced the incidence of apnea, fever, and sepsis evaluations. A starting dose of 0.01 mcg/kg/min did not cause increased adverse effects.
This study assesses the relative performance characteristics of five established classification techniques on data collected using the P300 Speller paradigm, originally described by Farwell and ...Donchin (1988 Electroenceph. Clin. Neurophysiol. 70 510). Four linear methods: Pearson's correlation method (PCM), Fisher's linear discriminant (FLD), stepwise linear discriminant analysis (SWLDA) and a linear support vector machine (LSVM); and one nonlinear method: Gaussian kernel support vector machine (GSVM), are compared for classifying offline data from eight users. The relative performance of the classifiers is evaluated, along with the practical concerns regarding the implementation of the respective methods. The results indicate that while all methods attained acceptable performance levels, SWLDA and FLD provide the best overall performance and implementation characteristics for practical classification of P300 Speller data.
There is a lack of high-resolution records of hydroclimate variability in the Eastern Mediterranean from the late glacial and early Holocene. More knowledge of the speed of climate shifts and the ...degree to which they were synchronous with changes in the North Atlantic or elsewhere is required to understand better the controls on Eastern Mediterranean climate. Using endogenic carbonate from a sediment sequence from Nar Gölü, a maar lake in central Turkey, dated by varve counting and uranium-thorium methods, we present high-resolution (∼25 years) oxygen (δ18O) and carbon isotope records, supported by carbonate mineralogy data, spanning the late glacial and Holocene. δ18Ocarbonate at Nar Gölü has been shown previously to be a strong proxy for regional water balance. After a dry period (i.e. evaporation far exceeding precipitation) in the Younger Dryas, the data show a transition into the relatively wetter early Holocene. In the early Holocene there are two drier periods that appear to peak at ∼9.3 ka and ∼8.2 ka, coincident with cooling ‘events’ seen in North Atlantic records. After this, and as seen in other records from the Eastern Mediterranean, there is a millennial-scale drying trend through the Mid Holocene Transition. The relatively dry late Holocene is punctuated by centennial-scale drought intervals, at the times of 4.2 ka ‘event’ and Late Bronze Age societal ‘collapse’. Overall, we show that central Turkey is drier when the North Atlantic is cooler, throughout this record and at multiple timescales, thought to be due to a weakening of the westerly storm track resulting from reduced cyclogenesis in the North Atlantic. However, some features, such as the Mid Holocene Transition and the fact the early Holocene dry episodes at Nar Gölü are of a longer duration than the more discrete ‘events’ seen in North Atlantic records, imply there are additional controls on Eastern Mediterranean hydroclimate.
•Sub-centennial resolution late glacial and Holocene isotope record from Turkey.•Rapid transition from a dry late glacial into a wet early Holocene.•Drier anomalies apparently at times of 9.3 ka and 8.2 ka events but last longer at Nar.•Droughts at times of 4.2 ka event and Late Bronze Age societal ‘collapse’.•Strong teleconnection with North Atlantic, but additional other drivers.
We describe a study designed to assess properties of a P300 brain–computer interface (BCI). The BCI presents the user with a matrix containing letters and numbers. The user attends to a character to ...be communicated and the rows and columns of the matrix briefly intensify. Each time the attended character is intensified it serves as a rare event in an oddball sequence and it elicits a P300 response. The BCI works by detecting which character elicited a P300 response. We manipulated the size of the character matrix (either 3
×
3 or 6
×
6) and the duration of the inter stimulus interval (ISI) between intensifications (either 175 or 350
ms). Online accuracy was highest for the 3
×
3 matrix 175-ms ISI condition, while bit rate was highest for the 6
×
6 matrix 175-ms ISI condition. Average accuracy in the best condition for each subject was 88%. P300 amplitude was significantly greater for the attended stimulus and for the 6
×
6 matrix. This work demonstrates that matrix size and ISI are important variables to consider when optimizing a BCI system for individual users and that a P300-BCI can be used for effective communication.
Restoration is a means for achieving and sustaining social-ecological system recovery.Failing to plan for both longer-term social and ecological impacts compromises the chances of attaining the ...intended benefits.Equity and power dynamics are crucial social dimensions to be considered in restoration. Integrating goals, metrics, and activities acknowledging power asymmetries and different types of equity must be done early on and throughout restoration design and evaluation.A logic model applied to restoration can help identify indicators that reflect the necessary inputs and activities to achieve the desired outputs, outcomes, and impacts that encompass social, economic, and ecological dimensions.We must shift attention from a project-based lens to situating restoration as a process within broader social-ecological systems to achieve lasting transformational change.
Ecosystem restoration conventionally focuses on ecological targets. However, while ecological targets are crucial to mobilizing political, social, and financial capital, they do not encapsulate the need to: integrate social, economic, and ecological dimensions and systems approaches; reconcile global targets and local objectives; and measure the rate of progress toward multiple and synergistic goals. Restoration is better conceived as an inclusive social-ecological process that integrates diverse values, practices, knowledge, and restoration objectives across temporal and spatial scales and stakeholder groups. Taking a more process-based approach will ultimately enable greater social-ecological transformation, greater restoration effectiveness, and more long-lasting benefits to people and nature across time and place.
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